Each of the component projects of this program project application involves the theoretical design of dosing regimens that would result in a particular drug exposure. The experimental implementation of those dosing regimens and the validation that experimentally achieved exposures approximate those that were intended are an integral part of each project. This overarching strategy applies to both the in vitro hollow fiber studies and in vivo animal studies proposed in the component studies. Validation of experimentally acheived exposures is accomplished by sampling over the course of the experiment for the purpose of measuring drug concentrations at appropriate time points. The timely, accurate and cost-efficient assay of the antibiotic and antiviral agents to be used in these studies in sample matrices such as complex growth media and animal serum and tissues lies outside the experience of most biomedical scientists. The presence of an in-house analytical core facility that can meet those objectives, serve as a resource in the planning of studies and maintain a collegial relationship with the investigators is crucial to the success of the proposed studies. It is therefore proposed that an analytical core support the investigators participating in this program project. The sevices provided by the analytical core include the development and validation of assays for each drug used in these projects, providing assistance to the investigators in designing preliminary experiments that verify the fidelity with which the hollow fiber system simulates the agent's pharmacokinetics and providing advice regarding the fabrication and setup of hollow fiber systems, particularly if modifications are required to optimize the application of the systems to a particular study.